Perturbing　the　periodic　electronic　structure　of　the　MoS2　basal　plane　via　vacancy　engineering　offers　an　opportunity　to　explore　its　intrinsic　activity.　A　significant　challenge　is　the　design　of　vacancy　states,　which　include　its　type,　distribution,　and　accessibility.　Here,　well-dispersed　and　vertically　aligned　MoS2　nanosheets　with　an　in-plane　selectively　cleaved　Mo−S　bond　on　a　carbon　matrix　(c-MoS2−C)　have　been　prepared　by　a　self-engaged　strategy,　which　synergistically　realizes　uniform　vacancy　manufacturing　and　three-dimensional　(3D)　self-assembly　of　the　defective　MoS2　nanosheets.　X-ray　adsorption　spectroscopy　investigation　confirms　that　the　cleaved　MoS2　basal　plane　generates　newly　active　edge　sites,　where　the　Mo　centers　feature　unsaturated　coordination　geometry.　Theoretical　calculations　reveal　that　the　exposed　interior　edge　Mo　sites　represent　new　active　centers　for　hydrogen　adsorption/desorption.　As　expected,　the　synthesized　c-MoS2−C　exhibits　markedly　enhanced　hydrogen　evolution　activity　and　superior　stability.　This　in-plane　activation　strategy　could　be　extended　to　other　types　of　transition-metal　dichalcogenides　and　catalytic　reaction　systems.　©　2021　American　Chemical　Society